The present invention relates generally to methods and apparatus for measuring the transmittance of blood within a retinal vessel and, more particularly, to methods and apparatus for accurately measuring the transmittance of blood within a retinal vessel by compensating for specular reflections from the apex of the retinal vessel and, in some embodiments, from edge portions of the retinal vessel.
A variety of spectroscopic oximetry techniques have been developed to monitor the transmittance of a blood sample. The transmittance of a blood sample is an important parameter since a number of other physiological parameters can be determined based upon the transmittance of a blood sample. For example, the absorbance of the blood sample and, in turn, the optical density of the blood sample can be readily determined based upon the transmittance of the blood sample. In addition, the blood oxygen saturation can be determined based upon the transmittance of the blood sample. By monitoring the blood oxygen saturation, the arteriovenous oxygen difference can be determined as described by U.S. Pat. No. 5,308,919 to Thomas E. Minnich. Based upon the arteriovenous oxygen difference, changes in the cardiac output of a patient can be determined to assist the post-operative monitoring and the management of critically ill patients. By monitoring the blood oxygen saturation, the loss of blood can also be detected and the rate and quantity of blood loss over time can be estimated as described in U.S. Pat. No. 5,119,814 to Thomas E. Minnich.
Conventional spectroscopic oximetry techniques measure the transmittance of a blood sample by illuminating the blood sample and measuring the intensity of the light which is transmitted through the blood sample. Based upon the intensity of the transmitted light, the transmittance of the blood sample can be determined.
These conventional spectroscopic oximetry techniques analyze blood that has been drawn from a patient and is disposed within a cuvette. Accordingly, the thickness of the sample and the concentration of the sample can be controlled to reduce the error in the measured transmittance. However, these spectroscopic oximetry techniques do require blood to be drawn from a patient to be analyzed. To develop a time history of the transmittance of a patient's blood so as to detect trends or changes in the transmittance of the blood over time, these conventional spectroscopic oximetry techniques require blood samples to be repeatedly drawn from a patient. In addition to the discomfort of the patient from which the blood is drawn, it quickly becomes a laborious and time consuming task to repeatedly draw blood samples from a patient and then to analyze each of the samples to determine the transmittance of the patient's blood over time. In addition, the transmittance of the blood cannot be analyzed in real time since the blood sample must be drawn and processed prior to measuring the transmittance of the blood sample.
Accordingly, a number of non-invasive retinal oximeters have been developed to measure the transmittance of the blood within a retinal vessel of a patient, thereby allowing a patient's blood to be analyzed in a non-invasive manner. For example, a retinal oximeter based upon photographic techniques is described by Dr. John B. Hickham, et al., in an article entitled A Study Of Retinal Venous Blood Oxygen Saturation In Human Subjects by Photographic Means, Circulation, Vol. 27, pp. 375-84 (March 1963). The retinal oximeter proposed by Hickham illuminates a retinal vessel with light having two different pairs of wavelengths, namely, light having a red/green pair of wavelengths, such as 640 nm and 510 nm, and light having a red/infrared pair of wavelengths such as 640 nm and 800 nm. The retinal oximeter proposed by Hickham also includes a fundus camera for exposing images of the illuminated optic nerve head directly to film. Once developed, the film density was measured at the center of a retinal vessel as well as on either side of the retinal vessel. For example, the film density can be measured, such as with a microdensitometer. Thus, the film density of the retinal vessel as well as the film density of the optic disk was measured.
By subtracting the film density of the retinal vessel from the film density of the optic disk, the retinal oximeter proposed by Hickham obtains a value proportional to the optical density of the retinal vessel. Since the light had actually propagated through the retinal vessel twice prior to being captured by the fundus camera, Hickham also proposed that the optical density of the retinal vessel obtained in the manner described above was actually equal to twice the actual optical density of the blood within the retinal vessel. See A. J. Cohen, et al., Multiple Scattering Analysis Of Retinal Blood Oximetry, IEEE, Trans. On Biomedical Engineering, Vol. 23, No. 5, pp. 391-400 (September 1976) which also describes a photographic eye oximeter which employs a modified fundus camera to obtain images of a retinal vessel at two different wavelengths of light, such as 470 nm and 515 nm.
As known to those skilled in the art, the light with which a retinal vessel is illuminated is not only transmitted through and absorbed within the retinal vessel, but is also specularly reflected from both the retinal vessel and the retinal background, such as the background fundus, on either side of the retinal vessel. If a significant portion of the light is reflected from either the retinal vessel or the background fundus on either side of the retinal vessel, the film density of the resulting image of the retinal vessel will not accurately depict the transmittance of the blood within the retinal vessel. Since the retinal oximeters proposed by Hickham and Cohen provide an image of a large portion of the retina, the operator of the retinal oximeter was able to select those portions of the resulting image which were least affected by specular reflections from either the retinal vessel or the background fundus. However, retinal oximeters based on photographic techniques, such as the retinal oximeters proposed by Hickham and Cohen are relatively difficult to automate since these techniques depend, at least in part, upon the operator's selection of the appropriate portion of the resulting image for analysis to determine a transmittance measurement which is not adversely affected by specular reflections from the retinal vessel or from the background fundus on either side of the retinal vessel.
Accordingly, scanning retinal oximeters have been developed to measure the transmittance of blood within a retinal vessel in an automated fashion. See, for example, U.S. Pat. No. 5,308,919 to Thomas E. Minnich which describes an eye oximeter for determining the arteriovenous oxygen difference by scanning the optic disk of a patient in a non-invasive manner.
In addition, F. C. Delori describes another scanning retinal oximeter in an article entitled Noninvasive Technique For Oximetry Of Blood In Retinal Vessels", Applied Optics, Vol. 27, No. 6, pp. 1113-25 (Mar. 15, 1988). The retinal vessel oximeter proposed by Delori includes a modified fundus camera which illuminates a retinal vessel with light having three wavelengths, such as 569.8 nm, 559.3 nm and 586.5 nm. The retinal vessel oximeter proposed by Delori scans the light across a retinal vessel and measures the intensity of the light transmitted through and reflected from the retinal vessel. As shown in FIG. 1, the intensity measured by the retinal oximeter proposed by Delori can be graphically illustrated as a function of retinal position. Based upon the measured intensity signals, the retinal oximeter proposed by Delori locates the retinal vessel by identifying the rising and falling edges of the intensity signal as the intensity signal crosses a vessel detection level. As shown in FIG. 1, the vessel detection level is typically set to seven-eighths of the mean value of the intensity signals measured by the retinal oximeter.
As also shown in FIG. 1, points b and g represent the points having the largest negative slope and the largest positive slope, respectively. Points a and h of FIG. 1 represent the boundary between the retinal vessel and the background fundus. Points a and h are typically determined as those points at which the absolute value of the slope of the signal intensity function becomes less than one-eighth of the absolute values of the minimum slope at point b and the maximum slope at point g, respectively. In addition, points d and e represent points having the minimum intensity within the retinal vessel. As discussed hereinafter, the upturned portion of the signal intensity graph between points d and e typically represents a specular reflection from the apex of the retinal vessel which can significantly diminish the accuracy with which a retinal oximeter determines the transmittance of a retinal vessel. As also shown in FIG. 1, points c and f are halfway between points b and d and points e and g, respectively.
The retinal oximeter proposed by Delori initially determines an average intensity value for the light reflecting from the background fundus by determining the average value of the intensity signals to the left of point a and to the right of point h. In other words, the retinal oximeter proposed by Delori determines the average intensity value for Region I of FIG. 1. In addition, the retinal oximeter proposed by Delori determines the average intensity of the light transmitted through the retinal vessel by determining the average value of the intensity signals between points c and d and between points e and f, i.e., the average value of the intensity signals within region II. As a result, the retinal oximeter proposed by Delori determines the transmittance of the blood within retinal vessel by dividing the average intensity of light transmitted through the retinal vessel by the average intensity of the light reflected from the background fundus.
Even though the retinal oximeter proposed by Delori determines the transmittance of blood within a retinal vessel in an automated fashion, the retinal oximeter proposed by Delori typically requires a relatively large number of scans to accurately determine the average values of the intensity of light transmitted through the retinal vessel and the intensity of light reflected from the background fundus. In addition, the retinal oximeter proposed by Delori generally requires a relatively large difference in contrast between the retinal vessel and the background fundus. It has been determined for light having many of the wavelengths useful for retinal oximetry, however, that the blood in relatively large retinal veins typically absorbs only about 15%. of the incident light, while the blood in relatively large retinal arteries absorbs only about 10% or less of the incident light. In addition, variations in the retinal pigmentation and the presence of underlying choroidal vessels frequently create variations in the intensity of the light reflected from the background fundus which are more pronounced than the variations in the intensity of the light transmitted through a retinal vessel. As a result, the retinal oximeter proposed by Delori which identifies a retinal vessel based upon a predetermined vessel detection threshold may not properly identify a retinal vessel and, as a result, may not accurately measure the transmittance of the retinal vessel.
As described above, it is oftentimes desirable to measure the transmittance of a blood sample in an accurate and timely manner. A number of invasive and non-invasive spectroscopic oximetry techniques have therefore been developed for determining the transmittance of a blood sample. However, a non-invasive retinal oximeter for determining the transmittance of the blood within a retinal vessel has not yet been developed which reduces or minimizes the errors in the measured transmittance which arise from specular reflections from the apex of the retinal vessel or from the opposed edge portions of the retinal vessel.